Role of adenosine and glycogen in ischemic preconditioning of rat hearts
European Journal of Pharmacology , Volume 414 - Issue 1 p. 55- 62
We tested whether ischemic preconditioning of the rat heart is mediated by reduced glycogenolysis during ischemia, an event triggered by adenosine A1 receptor activation. Rat hearts (n = 40) were studied with [31P] and [13C] nuclear magnetic resonance (NMR) spectroscopy, using the Langendorff perfusion technique (5.5 mM [1-13C]glucose, 10 U/l insulin). In parallel experiments, hearts (n = 43) were freeze-clamped at different time-points throughout the protocol. They were subjected to either ischemic preconditioning (PC), PC in the presence of 50 μM adenosine receptor antagonist, 8-(p-sulfophenyl)-theophylline (SPT), or intermittent infusion of 0.25 μM adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA). After 30 min ischemia and reperfusion, recovery of heart rate × pressure product was improved in hearts treated with preconditioning (33 ± 13%) or CCPA (58 ± 14%) compared with the SPT and ischemic control (IC) groups, which both failed to recover (P < 0.05). CCPA administration induced a 58% increase in pre-ischemic [13C]glycogen (P < 0.05 vs. all groups). In the PC and SPT groups, [13C]glycogen decreased by 25 and 47%, respectively (P < 0.05) due to the short bouts of ischemia, resulting in lower pre-ischemic glycogen compared to ischemic control and CCPA hearts (P < 0.05). The rate of [13C]glycogen utilization during the first 15 min of ischemia (in μmol/min g wwt) was not statistically different between IC (0.42 ± 0.03), PC (0.30 ± 0.04), and CCPA (0.38 ± 0.05) hearts, but was reduced in SPT hearts (0.24 ± 0.05; P < 0.05). Total glycogen depletion during 30-min ischemia was reduced in PC hearts (0.61 mg/g wwt) compared to IC (1.84 mg/g wwt) and CCPA (1.75 mg/g wwt) hearts; SPT did not block reduced glycogenolysis during ischemia in PC hearts (0.77 mg/g wwt vs. IC). This study adds further strong evidence that in rat hearts, adenosine is involved in ischemic preconditioning. However, protection is unrelated to pre-ischemic glycogen levels and glycogenolysis during ischemia.
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|Organisation||Department of Cardiology|
de Jonge, R, de Jong, J.W, Giacometti, D, & Bradamante, S. (2001). Role of adenosine and glycogen in ischemic preconditioning of rat hearts. European Journal of Pharmacology, 414(1), 55–62. doi:10.1016/S0014-2999(00)00875-X